Prokinetics in SIBO & Motility Disorders

Transcription

1 Prokinetics in SIBO & Motility Disorders Allison Siebecker ND, MSOM, LAc Source: boundless.com Motility Bootcamp, July 2016 AANP, Salt Lake City Ut Prokinetics: Definition Increase transit/motility in GI tract Improve coordination of GI movement Increase LES tone, relax pylorus v Amplify & coordinate GI muscular contractions Can have different sites of action: upper or lower GI Vs Laxative = stimulate BM s, loosen stool Pk can be laxative but often aren t, esp at low dose Pk can be used w/diarrhea to (+) upper GI motility, esp at lower dose Key Points Not all prokinetics are unsafe Side Effects/Reactions are common 1

2 Adapted from Scarpignato 98 and 12, with Ottillinger 13 Prucalopride no no yes yes few Iberogast yes yes yes few Prucalopride helps: nausea, bloating, pain, constipation (Emmanuel 12, Diederen 15) Iberogast helps: nausea, GERD, bloating, cramping/pain, constipation, diarrhea (Ottillinger 13) Prokinetics: Mechanisms of Action Muscarinic Acetylcholine Receptor Agonist: M (+) Acetylcholinesterase Inhibitor: ACh (-) Dopamine 2 Receptor Antagonist: D2(-) Seratonin 3 Receptor Antagonist: 5-HT3 (-) Seratonin 4 Receptor Agonist: 5-HT4 (+) = (+) ACh Motilin Receptor Agonist Cholecystokinin A Receptor Antagonist: CCK-A (-) Opioid Receptor Antagonist Adapted from Scarpignato 98 with Manabe 10, Simmen 06 M3 Opioid receptor receptor agonism antagonism Prucalopride no no yes no no no no Iberogast no yes yes no no yes yes Low Dose Naltrexone no no no no no no yes 2

3 Prokinetic Usage 1. Symptom Relief in Motility or Functional GI Disorders Dosed: tid before meals. Or after/in between meals and first a.m. for GERD, dyspepsia/gastroparesis (sx after meals), bloating v to move food, acid, gas out of St/SI Dosed: qd may enough for constipation depending on Pk Dose: standard Pk dose 2. Prevention of SIBO Relapse (maintenance of remission) Dosed: before bed v to (+) MMC overnight Dose: low dose to prevent return of sx Prokinetics Usage 1. Symptom Relief TID (or QD constipation) Regular dose 2. SIBO Relapse Prevention HS Low Dose Prokinetic Dose Motility, FGI Disorders Sx Relief Pharmaceutical Low Dose Erythromycin (LDE) mg tid-qid Prucalopride 1-4mg qd or 1mg bid-tid Low Dose Naltrexone (LDN) mg hs or bid 2.5mg- diarrhea, 4.5mg- constipation Herbal Iberogast 20 drops tid or PRN Ginger 500mg tid, 1000mg bid MP 2-3caps bid-tid (5Htp, Acetyl L Carnitine, Ginger, Vit C, B6) 3

4 Prokinetic Dose SIBO Relapse Prevention Pharmaceutical Low Dose Erythromycin (LDE) mg at bedtime (hs) Low Dose Prucalopride (LDP) 0.5 mg hs (up to 2 mg if needed) Low Dose Naltrexone (LDN) mg hs or bid 2.5mg- diarrhea, 4.5mg- constipation Herbal Iberogast drops hs Ginger 1000mg hs MP 2-3caps hs or hs & a.m. (5Htp, Acetyl L Carnitine, Ginger, Vit C, B6) Erythromycin & Prucalopride LDE No/weak Abx activity at low dose. Standard Tx for Gastroparesis Delayed SIBO relapse by 2.5 mo (Pimentel 09) SE vary. Tolerance possible. Prolong QT waves. P450 3A4 interactions Prucalopride Safer/stronger alternative to Tegaserod which delayed SIBO relapse by 6mo (Pimentel 09) Dr P thinks may help heal MMC over time. 1 st choice of many GE/most effective Pk SE: h/a, urinary urge, temporary diarr, varied. Tolerance possible. Obtained through Canadadrugs.com. Available in US soon. LDN & Iberogast LDN 68% success for SIBO Prevention, 38% failure (Ploesser 10) v Doesn t work as Pk (not strong enough) in many (Combine w/other Pk) SE: varied, sleep disturbance- titrate up to help avoid Also used for inflammation, depression, Auto Immune dz (=PI-IBS) Iberogast 75-85% success= IBS, Significant Sx improvement= Dyspepsia (Ottillinger) v Miracle for nausea More effective vs metoclopramide, similar vs cisapride = Dyspepsia SE: 0.04%. Safe for long term use, pregnancy, children 4

5 Ginger Ginger & MP MoA: + gastric emptying/mmc, M Rec (+), 5-HT3 (-) (Micklefield 99, Hu 11, Haniadka 13, Wu 08 Thompson 14) SE: 28% GERD/Ginger Burn (Thompson 14) helped by drinking water MP (no studies) Ginger, 5HTP, acetyl L-carnitine, Vit C, B6 MoA: saa + extra ACh/Cholinergic SE: GERD, diarrhea (+ LI motility too) Japanese Daikenchuto Motilin agonist + lots more (Tominaga 13, Nagano 99, Mochiki 10) Thought to effect distal SI & LI best (Nakaji 11) 190mg/kg/day (Endo 14) or 5g tid before meals Processed Ginger 3-5g + Ginseng 3g + Sichuan Pepper (Zanthoxylum piperitum) 2g Bitter Orange (immature/fructus auranti /Zhi Shi)(poncirus fructus) 5-HT4 (+) (Qiu 11, Jiang 14, Kim 13, Shim 10) ingredient in Chaihu Shugan San Triphala Other Natural Prokinetics mild prokinetic, laxative (Mukherjee 97, Jirankalgikar 12, Tamhane 97) How To Choose Pk v When you need to be sure: choose Pruc or LDE Pruc: need effectiveness, chronic cases, constipation, PI-IBS LDE: chronic/recurrent cases w/o constipation, gastroparesis LDN: inflammation, auto-immunity, depression Iberogast: want natural, broad sx relief, nausea Ginger: nausea/gastroparesis, not w/gerd MP: constipation, depression, not w/gerd v PARQ patient & ask their input 5

6 Pk PARQ: Pro s & Con s Prucalopride: Pro: strongest, safe (no QT/p450), low se, may heal MMC over time. Con: tolerance/se possible, expensive, 3wks to get in mail/not FDA approved Eryth: Pro: studied for SIBO, inexpensive/easily available, low se. Con: tolerance/se possible, long-term low-dose Abx, p450 interactions. Cx: preexist Ht cond (can prolong QT), w/berb (p450) LDN: Pro: anti-inflam, used for AI dz & depression, natural MoA. Con: not strong enough for some (1/3+)(tech not Pk), se: sleep disturbance Iberogast: Pro: natural, well studied as a Pk, broad GI sx relief, safe: kids, preg, lactation, no s.e. s in studies. Con: not strong enough for many, indiv se poss Ginger: Pro: natural, anti-nausea/inflam. Con: se: GERD/ginger burn, tolerance, not strong enough for many MP: Pro: (+)BM s/li motility, anti-depressant/sleep aid Con: (+)BM s/li motility, se: GERD/ginger burn, emotional, sleep, not strong enough for many Start/Duration/Stop Start: Sx Relief- any time Dr Scarp suggests LI purging 1 st to avoid anti-peristalsis (not w/diarrhea pt) Start: SIBO prevention- 1-5 days after tx Important to be on Pk between tx courses to hold gains/prevent relapse Plan ahead: Give the Rx/Pk Plan when Tx is given Duration: Sx- ongoing PRN. SIBO- min 3mo, ongoing for many May be stopped at any time- only risk is relapse of Sx or SIBO Stop: Titrate down slowly, esp w/sibo to catch a relapse Other Motility Considerations Stress Decrease stress/sympathetic: Rushing, worrying Increase parasympathetic: Conscious breaths, Gratitude, Rest Meal Spacing/ Overnight Fast 4-5 hrs between meals, 12 hr overnight fast to optimize MMC Physical Tx/Body work Wurn technique, visceral manipulation, cranial osteopathy 6

7 Pk: Pregnancy, Lactation & Pediatrics Preg & Lact: There are no category listing for the low Rx Pk doses used LDE (Cat B at regular Abx dose) Prucalopride is analogous to US Cat B (at regular 2-4mg dose) Safe: LDN, Iberogast, Ginger (max 2g/d) Peds Doses: LDE 25mg, LDN & Prucalopride 0.01mg/kg, Iberogast gtts, Ginger 250mg 7